Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

Abstract

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m 2 DOC plus 70 mg/m 2 CDDP on day 1 plus 700 mg/m 2 5-FU on days 1-5 at 4-week intervals.This regimen was tolerable and highly active. A phase II study has been started. In recent years, a new combined chemotherapeutic regimen consisting of DOC, CDDP, and 5-FU (DCF) has received much attention for the treatment of esophageal cancer. 8 The DCF regimen exploits the strong clinical effects of each component. However, there are few reports describing the use of a combination of DOC, CDDP, and 5-FU (DCF) for esophageal carcinoma.9 Therefore, we conducted a phase I clinical trial of a DCF regimen in patients with advanced esophageal carcinoma. Our aim was to determine the recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of DCF combination chemotherapy for patients with esophageal carcinoma. Secondary objectives were to assess treatment-related toxicity and efficacy. Patients and MethodsThis open-label, prospective, phase I study was conducted at Dokkyo Medical University Hospital, Tochigi, Japan. The institutional review board of Dokkyo Medical University approved this study, and all patients gave written informed consent before enrollment.Patients aged 20 to 75 years with a measurable target lesion pathologically confirmed as squamous cell carcinoma (SCC) or adenocarcinoma, which was surgically unresectable or recurrent, were eligible. They also had to have an ECOG performance status of 0, 1, or 2, a life expectancy of .12 weeks, and adequate liver, bone marrow, renal, and cardiovascular function (serum bilirubin 1.5 mg/dL; neutrophil count, 2000/mm 3 ; serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper limit of normal; alkaline phosphatase (ALP) 2.5 times the upper limit of normal, platelet count .10 3 10 4 /mm 3 ; hemoglobin 9.5 g/dL; and creatinine 1.2 mg/dL. The last chemotherapeutic treatment had to be at least 4 weeks before trial enrollment. Patients were excluded for the following reasons: known sensitivity to DOC, CDDP, 5-FU, or polysorbate 80; presence of other severe diseases, including malignant hypertension, severe heart failure, liver failure, and liver cirrhosis; inadequately controlled diabetes mellitus or bleeding disorders; current infectious disease with fever; presence of motor paralysis, p...

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil

“…Regimen of induction DCF and following curative therapy. The DCF regimen consisted of 70 mg/m 2 of docetaxel infused over 1 h on day 1, followed by 70 mg/m 2 of cisplatin infused over 1 hour on day 1, and 700 mg/m 2 of 5-FU on days 1 to 5 as a 24 h continuous intravenous infusion (20). This regimen was administered at 4-week intervals, two courses being administered before curative therapy (esophagectomy or definitive chemoradiotherapy).…”

Prevention of the Chemotherapy-Induced Oral Mucositis in Esophageal Cancer by Use of Hangeshashinto (TJ-14)

“…[4][5][6] In our institute, DCF is the first choice for preoperative CT to treat advanced EC. 7 However, DCF can cause various adverse events, including nausea, vomit, appetite loss, general fatigue, leukopenia, neutropenia, anemia, thrombocytopenia, febrile neutropenia, oral mucositis, diarrhea, and acute kidney injury. Among these toxicities, oral mucositis, which reportedly occurs in 7.1%-27.8% of CT/CRT-treated EC, causes pain and appetite loss, which impair patients' social interactions, make continuation of CT difficult and increase the likelihood of refusal of treatment, in addition to the physical pain.…”

“…Among these toxicities, oral mucositis, which reportedly occurs in 7.1%-27.8% of CT/CRT-treated EC, causes pain and appetite loss, which impair patients' social interactions, make continuation of CT difficult and increase the likelihood of refusal of treatment, in addition to the physical pain. 3,6,7 Kampo, traditional Japanese medicine, is made by mixing crude drugs. Hangeshashinto (TJ-14) is a Japanese traditional medicine that is effective for oral mucositis other than diarrhea, indigestion, hangover, heartburn, and gastritis.…”